Ionic and signal transduction alterations in Alzheimer's disease: relevance of studies on peripheral cells

Several lines of evidence indicate that Alzheimer's disease (AD) has systemic expression. Systemic changes are manifested as alterations in a number of molecular and cellular processes. Although, these alterations appear to have little or no consequence in peripheral systems, their parallel expression in the central nervous system (CNS) could account for the principal clinical manifestations of the disease. Recent research seems to indicate that alterations in ion channels, calcium homeostasis, and protein kinase C (PKC) can be linked and thereby constitute a model of pathophysiological relevance. Considering the difficulties of studying dynamic pathophysiological processes in the disease-ridden postmortem AD brain, peripheral tissues such as fibroblasts provide a suitable model to study molecular and cellular aspects of the disease.